Margherita Gobbo

A systematic review of therapeutical approaches in bisphosphonates-related osteonecrosis of the jaw (BRONJ)

OBJECTIVES The clinical management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains controversial. Since universally accepted guidelines have not been released yet, clinicians usually chose the type of treatment according to position papers based on expert opinion, or on empirical experience. The aim of this systematic review is to identify different therapeutical approaches for BRONJ that have been described in literature and to describe their effectiveness. MATERIALS AND METHODS A Medline via Pubmed and Scopus database literature search was conducted and all publications fulfilling the inclusion and exclusion criteria were included in eligibility assessment. The full texts of 146 retrieved articles were then screened and 40 studies were included in the quality assessment process. RESULTS After quality assessment, 22 full text articles were selected for the final review. 14 articles out of 22 were screened for stage-related outcomes. The overall outcome results and results for every disease stage were the highest when patients were treated with extensive surgery or extensive laser assisted surgery.

Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study

Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

Class IV laser therapy as treatment for chemotherapy-induced oral mucositis in onco-haematological paediatric patients: a prospective study

BACKGROUND Oral mucositis is a debilitating side effect of chemotherapy. Laser therapy has recently demonstrated efficacy in the management of oral mucositis (OM). AIM This prospective study was conducted to evaluate the efficacy of class IV laser therapy in patients affected by OM. DESIGN Eighteen onco-haematological paediatric patients receiving chemotherapy and/or haematopoietic stem cell transplantation, prior to total body irradiation, affected by OM, were enrolled in this study. Patients were treated with class IV laser therapy for four consecutive days; the assessment of OM was performed through WHO Oral Mucositis Grading Objective Scale, and pain was evaluated through visual analogue scale. Patients completed a validated questionnaire, and photographs of lesions were taken during each session. Patients were re-evaluated 11 days after the first day of laser therapy. RESULTS All patients demonstrated improvement in pain sensation, and all mucositis was fully resolved at the 11-day follow-up visit, with no apparent side effects. Laser therapy was well tolerated with remarkable reduction in pain associated with oral mucositis after 1-2 days of laser therapy. CONCLUSIONS Given class IV laser therapy appears to be safe, non-invasive, and potentially effective, prospective, randomized, controlled trials are necessary to further assess efficacy and to determine optimal treatment parameters.

Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

Evaluation of nutritional status in head and neck radio-treated patients affected by oral mucositis: efficacy of class IV laser therapy

PurposeTo retrospectively evaluate the role of class IV laser therapy in the amelioration of nutritional status of patients affected by oral mucositis due to radiotherapy of the head and neck region during oncological treatment.MethodsSixty-three oncological patients were included in this study. All patients were affected by tumors in the head and neck region and had developed oral mucositis during radiotherapy. Forty-two patients had been treated by high-power laser therapy whereas 21 patients had been managed with traditional medications. Data collection included weight measurement (kilogram) and body mass index (BMI) calculation (mass (kilogram)/(height) (square meter)) on the first and last day of radiotherapy. In addition, gender, age, pathology, and the kind of oncological treatment have been considered.ResultsLaser-treated patients decreased less in BMI during radiotherapy (p = 0.000). Patients treated by combined oncological treatments (radiotherapy and/or chemotherapy and/or surgery) had a higher weight loss during radiotherapy (p = 0.015). According to a multivariate regression analysis, the only variable which significantly influenced the reduction of BMI was laser treatment (p = 0.000).ConclusionsLaser therapy is actually considered one of the recommended remedies for the healing of oral mucositis due to cancer treatments. Healing of mucositis can deeply influence the feeding capacity of patients, through reduction of pain and improvement of chewing and swallowing capacities. It also allows lowering the costs for hospitalization and supportive care. Laser therapy should become part of nutritional interventions in oncological patients affected by oral mucositis.

Diagnostic and therapeutic features associated with modification of quality-of-life's outcomes between one and six months after major surgery for head and neck cancer

INTRODUCTION Treatments used in head and neck cancer greatly impact the physical, psychological and functional state of patients. Evaluation of quality of life has become an integral part of the treatment. OBJECTIVE This retrospective study evaluates features involved in changes in quality of life after major surgery for head and neck cancer within six months, according to self-reported outcomes. METHODS One hundred and thirty patients completed the University of Washington Quality of Life questionnaire one and six months after major surgery for head and neck cancer. A multivariate model was used to evaluate which diagnostic and therapeutic features were related to improvement of quality of life within a six-month period. RESULTS Significant improvement in most features related to quality of life was already recognizable at six months. Patients submitted to more invasive treatment had the biggest improvement in quality of life between time-points, as well as those patients with bigger tumors. CONCLUSION After major surgery, patients may undergo fast recovery, with overall quality of life likely to improve in the short-term. Clinicians must be aware of the importance of dealing with treatment-related issues immediately after surgery, with hopeful possibility of on-the-upgrade results.

Laser surgical treatment of chronic graft-versus-host disease (cGvHD)-induced buccal mucosal sclerosis

Abstract Oral sclerotic chronic graft-versus-host-disease (cGvHD) represents a distinctive phenotype of cGvHD which causes severe disability and morbidity due to impaired oral hygiene and food intake, jaw pain, tightness and discomfort. As it is a rare presentation, there is little published evidence on its management. Here, the case of a patient suffering from stage-2 oral sclerotic cGvHD treated with a bilateral surgical release of fibrous bands performed using a blue light-emitting diode laser (λ=445±5 nm) is presented. This was followed by maintenance of the mouth opening through a specifically designed resin intraoral device. After the laser-assisted surgical procedure, the patient did not experience any bleeding, pain or discomfort, and the mouth opening was increased from 12 mm to 20 mm. Over a 6-month follow-up period, the patient increased and stabilized the mouth opening from 20 mm to 25 mm helping to maintain and improve oral hygiene together with overall comfort and quality of life.

Methotrexate-induced oral mucositis in rheumatoid arthritis disease: Therapeutic strategy in a case report/Methotrexat-induzierte orale Mukositis bei rheumatoider Arthritis: Therapeutische Strategie in einem Fallbericht

Abstract Objective: The aim of this case report is to evaluate the efficacy of low-level laser therapy (LLLT) in the treatment of oral mucositis induced by methotrexate (MTX). Methods: A 52-year-old male patient, affected by rheumatoid arthritis and treated with corticosteroids and MTX, complained about severe oral pain and lesions for two months. He had been treated with topical and systemic corticosteroid therapy and chlorhexidine rinses with no significant improvement. He was not able to eat solid food or to wear his dental prosthesis. Examination of the oral cavity revealed retro-commissural and labial bilateral ulcerations and erythema and a 2-cm wide fibrous white lesion on the lower anterior vestibular ridge. Blood tests showed mild pancytopenia, and oral biopsies evidenced a “non-specific inflammatory condition” excluding any precancerous or paraneoplastic lesion or autoimmune diseases of the oral cavity. Previous medical records revealed that MTX had been discontinued many times due to mucositis since 2006, when the therapy had been started. This suggested a correlation between the onset of oral mucositis and MTX accumulation. LLLT was carried out for 4 consecutive days and three once-a-week follow-ups were performed. Results: Lesions had completely healed during the second follow-up and the patient referred no pain at all from the 4th laser session on, therefore, the discontinuation of MTX had not been necessary. Conclusion: LLLT could represent an innovative technique to relieve pain related to MTX side effects thus avoiding dangerous discontinuation of therapy. Zusammenfassung Ziel: Das Ziel dieses Fallberichtes ist es, die Wirksamkeit der Low-Level-Laser-Therapie (LLLT) in der Behandlung der Methotrexat (MTX)-induzierten oralen Mukositis zu bewerten. Methoden: Ein an rheumatoider Arthritis erkrankter und mit Corticosteroiden und MTX behandelter 52-Jahre alter Patient klagte über seit 2 Monaten anhaltende stark schmerzende Läsionen im Mund. Die topische und systemische Behandlung mit Corticosteroiden und Chlorhexidin-Spülungen führte zu keiner signifikanten Symptomverbesserung. Er war nicht mehr in der Lage, feste Nahrung zu essen oder seine Zahnprothese zu tragen. Die Untersuchung der Mundhöhle ergab retrokommissural und beidseitig labial Ulzerationen und Rötungen sowie eine 2 cm breite fibröse, weiße Läsion am unteren vorderen vestibulären Kieferkamm. Blutuntersuchungen zeigten eine milde Panzytopenie. Die bioptische Untersuchung ergab eine “nicht-spezifische entzündliche Erkrankung” unter Ausschluss von präkanzerösen oder paraneoplastischen Läsionen oder Autoimmunerkrankungen der Mundhöhle. Frühere medizinische Aufzeichnungen ergaben, dass seit Therapiebeginn 2006 die Behandlung mit MTX wiederholt wegen des Auftretens einer Mukositis unterbrochen werden musste. Dies legte nahe, dass ein Zusammenhang zwischen dem Auftreten einer oralen Mukositis und der MTX-Akkumulation besteht. Zur Therapie der Mukositis wurde an 4 aufeinanderfolgenden Tagen eine LLLT durchgeführt. Das Behandlungsergebnis wurde über einen Zeitraum von 3 Wochen (1x wöchentliche Visiten) kontrolliert. Ergebnisse: Nach der 4. Laserbehandlung war der Patient schmerzfrei; während der 2. Nachkontrolle zeigte sich, dass die Läsionen vollständig abgeheilt waren. Aufgrund dieses Behandlungserfolges musste die MTX-Medikation nicht unterbrochen werden. Fazit: Die LLLT stellt eine innovative Therapiemöglichkeit dar, um Schmerzen im Zusammenhang mit MTX-Nebenwirkungen zu behandeln und somit das gefährliche Absetzen des Medikamentes zu vermeiden.

Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: LaMPO RCT

To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects.

Laser-induced immune modulation inhibits tumor growth in vivo (Conference Presentation)

Photobiomodulation stands as a recommended therapy for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. We assessed cancer cell metabolism and proliferation in vitro and in vivo after exposure to different laser protocols. We exploited both ectopic melanoma and a more physiological oral carcinogenesis mouse model, followed by molecular, histological and immunohistochemical characterization. Laser irradiation resulted in a slightly increase in cell metabolism and proliferation in vitro, albeit each protocol exerted a difference response. Of notice, in vivo laser light reduced tumour growth and invasiveness, indicating e beneficial effect on tumor microenvironment. Laser-treated tumors were surrounded and infiltrated by immune cells, mainly lymphocytes and dendritic cells, paralleled by an enhanced secretion of type I interferons. In contrast, the number of pro-angiogenic macrophages was reduced in response to laser irradiation, with consequent normalization of the tumor vasculature. Based on these finding we have also started exploring the effect of photobiomodulation on lymphocyte response in an experimental model of vaccination. Preliminary data indicate that laser light induced antigen-specific CD8+ and CD4+ T cell responses. In conclusion, our data point toward photobiomodulation as an effective strategy to boost the immune response in vivo, with relevant, therapeutic activities in both cancer and vaccination experimental models. These results support the safe use of laser light on cancer patients and open the way to innovative therapeutic opportunities.